Influenza is a serious world-wide concern that annually affects 20% of children and 5% of adults. Current vaccinations are effective for healthy adults, but offer a low rate of protection (<40%) for high risk groups including the very old, very young and immunocompromised. A better understanding of the factors affecting the establishment and quality of immunological memory to the virus is needed to design better therapies and preventative measures. We have developed a social stress model, Social Disruption (SDR), that induces glucocorticoid resistance in splenocytes and results in a significantly more reactive pro-inflammatory cytokine environment. Preliminary experiments show that when this stressor is applied prior to a primary influenza infection, there is faster cessation of viral replication and increased expression of type I interferons. During the memory phase, SDR mice have a greater delayed-type hypersensitivity response to a footpad antigen challenge. Upon reinfection/challenge, there is a more numerous virus-specific T cell response. The goal of this grant proposal is to determine the mechanisms by which this social stressor enhances the development of virus specific memory T cell responses. The inter-disciplinary research plan detailed in this application will lead to a more complex grasp of factors able to positively regulate the immune response to a viral challenge. [unreadable] [unreadable]